Project Summary Major biomedical discoveries continue to be made possible with advanced `omic technologies, and continued technological advances in `omic technologies are essential for a more complete physicochemical phenotyping (qualitative and quantitative characterizations) of normal and perturbed biological systems. Biological systems are overwhelming complex, and relatively subtle perturbations in the physicochemical status of these systems clearly lead to profound changes in the health of the organism. The Duke Proteomics and Metabolomics Shared Resource (DPMSR) is tasked with supporting the protein/peptide/metabolite characterization needs of the seven Basic Science Departments and the eleven Clinical Sciences Departments of the School of Medicine, as well as for Duke University as a whole. The DPMSR provides extensive capabilities for mass spectrometry based analyses, with the wide scope of capabilities required to support a variety of basic science studies and the significant scale of capacity to support clinical studies, specifically including biomarker discovery and biomarker verification experiments. The DPMSR has ~ $5,000,000 in dedicated analytical and informatic hardware/software, and a staff of nine, including four with PhDs and Research Faculty appointments. This proposal requests a mass spectrometer which is unique to Duke and to the surrounding region - an Orbitrap Fusion? Lumos? Tribrid? MS/MS mass spectrometer system from Thermo Scientific. While the DPMSR has a Q-Exactive Plus? and a Q- Exactive-HF?, the Lumos system is needed for its unique capabilities: multiplexed proteomics with accurate quantitation using Tandem Mass Tags via its MS3 capability; improved sensitivity and speed of analysis made possible by its combination of electrodynamic ion funnel and high-field orbitrap; and its combination of multiple fragmentation mechanisms ? CID, HCD, ETD, and EThCD. While the QE-HF also has the high- field orbitrap, the high ion flux from the electrodynamic ion funnel on the Lumos is required to fill the orbitrap at its maximum data acquisition rate of 20 Hz. The requested system will provide unique performance capabilities that are synergistically aligned with the existing LC-MS/MS systems and the comprehensive, dedicated informatics infrastructure in the DPMSR, enabling Duke to leverage to the fullest extent the extensive expertise, robust data analysis capabilities, and plethora of important NIH-funded biomedical research opportunities at Duke. Importantly, the projects listed in this proposal will support a diverse range of projects from PIs from the School of Medicine, the Duke Cancer Institute, the University Chemistry Department and the University Biomedical Engineering Department.